DNA Damage-Induced Neurodegeneration in Accelerated Ageing and Alzheimer’s Disease
DNA repair ensures genomic stability to achieve healthy ageing, including cognitive maintenance. Mutations on genes encoding key DNA repair proteins can lead to diseases with accelerated ageing phenotypes. Some of these diseases are xeroderma pigmentosum group A (XPA, caused by mutation of <i>...
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MDPI AG
2021-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/13/6748 |
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| author | Heling Wang Sofie Lautrup Domenica Caponio Jianying Zhang Evandro F. Fang |
| author_facet | Heling Wang Sofie Lautrup Domenica Caponio Jianying Zhang Evandro F. Fang |
| author_sort | Heling Wang |
| collection | DOAJ |
| description | DNA repair ensures genomic stability to achieve healthy ageing, including cognitive maintenance. Mutations on genes encoding key DNA repair proteins can lead to diseases with accelerated ageing phenotypes. Some of these diseases are xeroderma pigmentosum group A (XPA, caused by mutation of <i>XPA</i>), Cockayne syndrome group A and group B (CSA, CSB, and are caused by mutations of <i>CSA</i> and <i>CSB</i>, respectively), ataxia-telangiectasia (A-T, caused by mutation of <i>ATM</i>), and Werner syndrome (WS, with most cases caused by mutations in <i>WRN</i>). Except for WS, a common trait of the aforementioned progerias is neurodegeneration. Evidence from studies using animal models and patient tissues suggests that the associated DNA repair deficiencies lead to depletion of cellular nicotinamide adenine dinucleotide (NAD<sup>+</sup>), resulting in impaired mitophagy, accumulation of damaged mitochondria, metabolic derailment, energy deprivation, and finally leading to neuronal dysfunction and loss. Intriguingly, these features are also observed in Alzheimer’s disease (AD), the most common type of dementia affecting more than 50 million individuals worldwide. Further studies on the mechanisms of the DNA repair deficient premature ageing diseases will help to unveil the mystery of ageing and may provide novel therapeutic strategies for AD. |
| first_indexed | 2024-03-10T10:07:21Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T10:07:21Z |
| publishDate | 2021-06-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-3c489005aa9b4cdaaac37396eae91b052023-11-22T01:24:05ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-06-012213674810.3390/ijms22136748DNA Damage-Induced Neurodegeneration in Accelerated Ageing and Alzheimer’s DiseaseHeling Wang0Sofie Lautrup1Domenica Caponio2Jianying Zhang3Evandro F. Fang4Department of Clinical Molecular Biology, Akershus University Hospital, University of Oslo, 1478 Lørenskog, NorwayDepartment of Clinical Molecular Biology, Akershus University Hospital, University of Oslo, 1478 Lørenskog, NorwayDepartment of Clinical Molecular Biology, Akershus University Hospital, University of Oslo, 1478 Lørenskog, NorwayDepartment of Clinical Molecular Biology, Akershus University Hospital, University of Oslo, 1478 Lørenskog, NorwayDepartment of Clinical Molecular Biology, Akershus University Hospital, University of Oslo, 1478 Lørenskog, NorwayDNA repair ensures genomic stability to achieve healthy ageing, including cognitive maintenance. Mutations on genes encoding key DNA repair proteins can lead to diseases with accelerated ageing phenotypes. Some of these diseases are xeroderma pigmentosum group A (XPA, caused by mutation of <i>XPA</i>), Cockayne syndrome group A and group B (CSA, CSB, and are caused by mutations of <i>CSA</i> and <i>CSB</i>, respectively), ataxia-telangiectasia (A-T, caused by mutation of <i>ATM</i>), and Werner syndrome (WS, with most cases caused by mutations in <i>WRN</i>). Except for WS, a common trait of the aforementioned progerias is neurodegeneration. Evidence from studies using animal models and patient tissues suggests that the associated DNA repair deficiencies lead to depletion of cellular nicotinamide adenine dinucleotide (NAD<sup>+</sup>), resulting in impaired mitophagy, accumulation of damaged mitochondria, metabolic derailment, energy deprivation, and finally leading to neuronal dysfunction and loss. Intriguingly, these features are also observed in Alzheimer’s disease (AD), the most common type of dementia affecting more than 50 million individuals worldwide. Further studies on the mechanisms of the DNA repair deficient premature ageing diseases will help to unveil the mystery of ageing and may provide novel therapeutic strategies for AD.https://www.mdpi.com/1422-0067/22/13/6748DNA damageDNA repairAlzheimer’s disease (AD)age-related disease |
| spellingShingle | Heling Wang Sofie Lautrup Domenica Caponio Jianying Zhang Evandro F. Fang DNA Damage-Induced Neurodegeneration in Accelerated Ageing and Alzheimer’s Disease International Journal of Molecular Sciences DNA damage DNA repair Alzheimer’s disease (AD) age-related disease |
| title | DNA Damage-Induced Neurodegeneration in Accelerated Ageing and Alzheimer’s Disease |
| title_full | DNA Damage-Induced Neurodegeneration in Accelerated Ageing and Alzheimer’s Disease |
| title_fullStr | DNA Damage-Induced Neurodegeneration in Accelerated Ageing and Alzheimer’s Disease |
| title_full_unstemmed | DNA Damage-Induced Neurodegeneration in Accelerated Ageing and Alzheimer’s Disease |
| title_short | DNA Damage-Induced Neurodegeneration in Accelerated Ageing and Alzheimer’s Disease |
| title_sort | dna damage induced neurodegeneration in accelerated ageing and alzheimer s disease |
| topic | DNA damage DNA repair Alzheimer’s disease (AD) age-related disease |
| url | https://www.mdpi.com/1422-0067/22/13/6748 |
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